dbSNP rs2453839: IGFBP3:c.*16-140A>G (chr7-45913974-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000598.5(IGFBP3):c.*16-140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,086 control chromosomes in the GnomAD database, including 5,395 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5395 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

IGFBP3
NM_000598.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

Publications

36 publications found

Variant links:

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

IGFBP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	NM_000598.5	MANE Select	c.*16-140A>G		intron	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.*16-140A>G		intron	N/A	NP_001013416.1	P17936-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.*16-140A>G	intron	N/A	ENSP00000477772.2	P17936-1
IGFBP3	ENST00000908406.1		c.*16-140A>G	intron	N/A	ENSP00000578465.1
IGFBP3	ENST00000381083.9	TSL:5	c.*16-140A>G	intron	N/A	ENSP00000370473.4	P17936-2

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38098

AN:

151966

Hom.:

5383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.251

AC:

38135

AN:

152084

Hom.:

5395

Cov.:

AF XY:

0.248

AC XY:

18419

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.397

AC:

16448

AN:

41458

American (AMR)

AF:

0.163

AC:

2492

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

828

AN:

3470

East Asian (EAS)

AF:

0.198

AC:

1023

AN:

5170

South Asian (SAS)

AF:

0.181

AC:

870

AN:

4816

European-Finnish (FIN)

AF:

0.196

AC:

2073

AN:

10576

Middle Eastern (MID)

AF:

0.171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.202

AC:

13718

AN:

67990

Other (OTH)

AF:

0.226

AC:

478

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1439

2879

4318

5758

7197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

5773

Bravo

AF:

0.255

Asia WGS

AF:

0.196

AC:

678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.26

(source)

DANN

Benign

0.39

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over